Reversal of hepatotoxin-induced pre-fibrogenic events by Emblica officinalis--a histological study.

Efficacy of a herbal product of E. officinalis (fruit) (EO) has been evaluated against carbon tetrachloride (CCl4) and thioacetamide (TAA) induced changes in rat liver. Chronic treatment of CCl4 and TAA revealed abnormal histopathology indicative of pre-fibrogenic events. EO reversed such alterations with significant regenerative changes suggestive of its preventive role in prefibrogenesis of liver.

Nucleolus contains signal molecules that constitute membrane-nucleolus linked pathway

Since there have been very few studies on nucleolar signaling, an attempt was made to establish nucleolar signal pathways which link the cell membrane to the nucleolus for the transfer of extracellular signals. Two pathways were studied. One was the G alpha s mediated cAMP pathway where two signal molecules were yielded, including RII and protein kinase A. The other was the G alpha q mediated DAG/IP3 pathway which yields two signals including protein kinase C and IP3/Ca2+. By the studying isolated nucleoli from resting liver, regenerating liver or weak carcinogen thioacetamide treated liver, it was possible to detect protein kinase A (PKA), protein kinase C (PKC) and RII subunits. In addition, CK2 was detected. It was found that external signals transmitted through G protein coupled receptors could reach into the nucleolus and that physical translocation of signal molecules was an integral step involved in membrane-nucleolus linked pathways. When an in vitro assay of the above signal molecules was carried out using [gamma-32P]-ATP, most kinase dependent phosphorylation was via the major CK2 (more than 95%). Therefore, it is suggested that the major CK2 dependent pathway is involved in 'house keeping' for nucleolar integrity and the minor pathways, dependent on PKA, PKC and others, are involved in subtle regulatory mechanisms such as 'extra-house-keeping' activities by nucleolar chromosomal remodeling.

Thioacetamide effects on the polypeptidic and nucleoporin pattern and chemical composition of rat liver nuclear envelope subfractions

The effect of the administration of seven doses of the hepatocarcinogen thioacetamide on the chemical composition of rat liver nuclear envelope subfractions: associated chromatin, nuclear membranes and pore complex-lamina fraction, is analyzed. No alteration in DNA, RNA or phospholipid content is observed after the hepatocarcinogen treatment. Electrophoretic studies of each subfraction from thioacetamide treated rats show differences in the relative proportions of some polypeptides when compared with the controls. Examination of the wheat germ agglutinin binding polypeptides of each subfraction reveals a decrease in the stain of two pore complex-lamina nucleoporins of 85 and 164 kDa and an increase in one of 93 kDa; this observation can be due to changes in the quantity and/or in the agglutinin binding capacity of the nucleoporin as a result of thioacetamide administration. In view of the participation of nucleoporins in the nucleocytoplasmic transport, the changes observed suggest a relationship between changes of some O-linked N-acetyl glucosamine polypeptides components of the nuclear pore complex and the altered transport of some RNA species observed after thioacetamide administration.

detection of hepatic glucose phosphorylation enzymes in two strains of mice and their relation to thioacetamide effect on the liver

Hexokinase isoenzymes in the liver of two inbred strains of mice [C3H/He and C58] have been determined initially. Four isoenzymes catalyzing phosphorylation of glucose and designated GK, HKI, HKII and HKIII, were resolved by high performance liquid chromatography on DEAE-cellulose columns of liver extracts from C3H/He and C58 mice. The enzymes were identified by their activity and in a series of immunological tests including immunoelectrophoresis and immunoprecipitation. In untreated mice, the glucokinase [GK] activity was predominant and the three hexokinases [HKI, HKII and HKIII] detected were characterized by low activities. However, intraperitoneal injection of thiocetamide resulted in a significant decrease in the glucokinase activity and in an increase in hexokinases activity, especially that of hexokinases II and III. While confirming the presence of hexokinase III in mice livers, the present work also provides for a significant improvement in the detection of hexokinase III in mice and presents an interesting observation on the effect of thiocetamide on the liver